(1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate | 148702-58-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate
• 英文别名: SB 204070；SB 204070 hydrochloride；(1-butylpiperidin-4-yl)methyl 5-amino-6-chloro-2,3-dihydro-1,4-benzodioxine-8-carboxylate
• CAS: 148702-58-3
• 化学式: C₁₉H₂₇ClN₂O₄
• 分子量: 382.887
• InChiKey: AOOSJYIINXVNHV-UHFFFAOYSA-N

物化性质

• 熔点：
  243-245 °C(lit.)
• 溶解度：
  H2O:20 mg/mL加热

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 (1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate 在 lithium nitride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 (1-butylpiperidin-4-yl)methyl 6-chloro-5-((111C)methylamino)-2,3-dihydro-1,4-benzodioxine-8-carboxylate
  参考文献：
  名称：

  选择性高亲和力 5-HT4 受体配体的合成、结构-亲和力关系和放射性标记作为正电子发射断层扫描的前瞻性成像探针

  摘要：

  在寻找可用作放射性配体的高亲和力受体配体，用于使用正电子发射断层扫描 (PET) 在体内成像脑 5-HT 4受体时，对高亲和力 5-HT 4拮抗剂进行了结构修饰(1-丁基哌啶-4-基)甲基 8-氨基-7-碘-2,3-二氢苯并[ b ][1,4]二恶英-5-羧酸酯 ( 1 , SB 207710)。这些修饰主要在酯键的芳基侧进行，以允许用正电子发射体快速标记羧酸组分，碳 11 ( t 1/2 = 20.4 min) 或氟 18 ( t 1/2= 109.7 分钟），并且包括 (i) 用小的取代基如腈、甲基或氟取代碘原子，(ii) 8-氨基的甲基化，(iii) 二恶烷环的打开，以及（ iv) N-烷基组长度的改变。发现了重组人 5-HT 4受体的高亲和力配体，这些配体适合用正电子发射体进行标记，并且具有作为成像探针的开发潜力。开环放射性配体（（[甲氧基- 11 C]1-丁基哌啶-4-基）4-氨基-3-甲氧基苯甲酸甲酯；[

  DOI：

  10.1021/jm100668r
• 作为产物：
  描述：

  8-acetamido-1,4-benzodioxane-5-carboxylic acid 在 sodium hydroxide 、 水 、 甲基锂 、 氯 、 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 生成 (1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate
  参考文献：
  名称：

  （1-丁基-4-哌啶基）甲基8-氨基-7-氯-1,4-苯并二恶烷-5-羧酸盐酸盐：一种高效且选择性的从甲氧氯普胺衍生的5-HT4受体拮抗剂。

  摘要：

  DOI：

  10.1021/jm00077a018

文献信息

• Novel esters of 1, 4-disubstituted piperidine derivatives
  申请人：——

  公开号：US20020042430A1

  公开（公告）日：2002-04-11

  This invention concerns the compounds of formula 1 the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein R 1 is C 1-6 alkyloxy, C 2-6 alkenyloxy or C 2-6 alkynyloxy; R 2 is hydrogen or C 1-6 alkyloxy, or when taken together R 1 and R 2 may form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C 1-6 alkyl, R 3 is hydrogen or halo; L is C 3-6 cycloalkyl, C 5-6 cycloalkanone, C 2-6 alkenyl optionally substituted with aryl, or L is a radical of formula —Alk—R 4 , —Alk—NR 5 R 6 , 1-R 6 -4-piperidinyl, Alk—X—R 7 , —Alk—Y—C(═O)—R 9 , or —Alk—Y—C(═O)—NR 11 R 12 wherein each Alk is C 1-12 alkanediyl; R 4 is hydrogen, C 1-6 alkylsulfonylamino, C 3-6 cycloalkyl, C 5-6 cycloalkanone, Ar—, di(Ar)methyl, Ar—oxy- or Het 1 ; R 5 is hydrogen or C 1-6 alkyl; R 6 is Het 2 ; R 7 is hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 cycloalkyl, Ar or Het 2 ; X is O, S, SO 2 or NR 8 ; said R 8 being hydrogen, C 1-6 alkyl or Ar; R 9 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, Ar, ArC 1-6 alkyl, di(Ar)methyl, C 1-6 alkyloxy or hydroxy; Y is NR 10 or a direct bond; said R 10 being hydrogen, C 1-6 alkyl or Ar; R 11 and R 12 each independently are hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, Ar or ArC 1-6 alkyl, or R 11 and R 12 combined with the nitrogen atom bearing R 11 and R 12 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C 1-6 alkyl, amino or mono or di(C 1-6 alkyl)amino, or said R 11 and R 12 combined with the nitrogen bearing R 11 and R 12 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C 1-6 alkyl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及公式1的化合物，其N-氧化物形式，药学上可接受的酸加成盐和立体化学异构体形式，其中R1是C1-6烷氧基，C2-6烯氧基或C2-6炔氧基；R2是氢或C1-6烷氧基，或当R1和R2一起取时，它们可以形成公式的双价基团，在所述双价基团中，一个或两个氢原子可以被C1-6烷基取代，R3是氢或卤素；L是C3-6环烷基，C5-6环烷酮，C2-6烯基，可选地取代芳基，或L是公式—Alk—R4，—Alk—NR5R6，1-R6-4-哌啶基，Alk—X—R7，—Alk—Y—C(═O)—R9或—Alk—Y—C(═O)—NR11R12的基团，其中每个Alk是C1-12烷二基；R4是氢，C1-6烷基磺酰胺基，C3-6环烷基，C5-6环烷酮，Ar—，二(Ar)甲基，Ar—氧基或Het1；R5是氢或C1-6烷基；R6是Het2；R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基，Ar或Het2；X是O，S，SO2或NR8；所述的R8是氢，C1-6烷基或Ar；R9是氢，C1-6烷基，C3-6环烷基，Ar，ArC1-6烷基，二(Ar)甲基，C1-6烷氧基或羟基；Y是NR10或直接键；所述的R10是氢，C1-6烷基或Ar；R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，Ar或ArC1-6烷基，或R11和R12与携带R11和R12的氮原子结合，可以形成一个吡咯啉基或哌啶基，两者都可以选择地取代C1-6烷基，氨基或单或双(C1-6烷基)氨基，或所述的R11和R12与携带R11和R12的氮原子结合，可以形成一个哌嗪基或4-吗啉基基团，两者都可以选择地取代C1-6烷基。公开了制备所述产品的过程，包括所述产品的配方以及它们作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。
• Novel N-substituted 4-((-4'-aminobenzoyl)-oxymethyl)-piperidines having gastric prokinetic properties
  申请人：——

  公开号：US20030153573A1

  公开（公告）日：2003-08-14

  This invention concerns the compounds of formula 1 the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein R 1 is C 1-6 alkyloxy, C 2-6 alkenyloxy or C 2-6 alkynyloxy; R 2 is hydrogen or C 1-6 alkyloxy, or when taken together R 1 and R 2 may form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C 1-6 alkyl, R 3 is hydrogen or halo; L is C 3-6 cycloalkyl, C 5-6 cycloalkanone, C 2-6 alkenyl optionally substituted with aryl, or L is a radical of formula -Alk—R 4 , -Alk—NR 5 R 6 , 1-R 6 -4-piperidinyl, Alk-X—R 7 , -Alk—Y—C(═O)—R 9 , or -Alk—Y—C(═O)—NR 11 R 12 wherein each Alk is C 1-12 alkanediyl; R 4 is hydrogen, C 1-6 alkylsulfonylamino, C 3-6 cycloalkyl, C 5-6 cycloalkanone, Ar-, di(Ar)methyl, Ar-oxy- or Het 1 ; R 5 is hydrogen or C 1-6 alkyl; R 6 is Het 2 ; R 7 is hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 cycloalkyl, Ar or Het 2 ; X is O, S, SO 2 or NR 8 ; said R 8 being hydrogen, C 1-6 alkyl or Ar; R 9 is hydrogen, C 1-6 alkyl, C 3-6 cyclo-alkyl, Ar, ArC 1-6 alkyl, di(Ar)methyl, C 1-6 alkyloxy or hydroxy; Y is NR 10 or a direct bond; said R 10 being hydrogen, C 1-6 alkyl or Ar; R 11 and R 12 each independently are hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, Ar or ArC 1-6 alkyl, or R 11 and R 12 combined with the nitrogen atom bearing R 11 and R 12 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C 1-6 alkyl, amino or mono or di(C 1-6 alkyl)amino, or said R 11 and R 12 combined with the nitrogen bearing R 11 and R 12 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C 1-6 alkyl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及公式1的化合物，其N-氧化物形式，药学上可接受的酸加成盐和其立体化学异构体形式，其中R1是C1-6烷氧基，C2-6烯氧基或C2-6炔氧基; R2是氢或C1-6烷氧基，或当R1和R2一起取时，它们可以形成公式的二价基团，在所述的二价基团中，一个或两个氢原子可以被C1-6烷基取代，R3是氢或卤素; L是C3-6环烷基，C5-6环戊酮，C2-6烯基，可选地用芳基取代，或L是公式-Alk-R4，-Alk-NR5R6，1-R6-4-哌啶基，Alk-X-R7，-Alk-Y-C(═O)-R9，或-Alk-Y-C(═O)-NR11R12的基团，其中每个Alk是C1-12烷二基基；R4是氢，C1-6烷基磺酰胺基，C3-6环烷基，C5-6环戊酮，Ar-，二(Ar)甲基，Ar-氧基或Het1; R5是氢或C1-6烷基；R6是Het2; R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基，Ar或Het2; X是O，S，SO2或NR8; R8是氢，C1-6烷基或Ar; R9是氢，C1-6烷基，C3-6环烷基，Ar，ArC1-6烷基，二(Ar)甲基，C1-6烷氧基或羟基; Y是NR10或直接键; R10是氢，C1-6烷基或Ar; R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，Ar或ArC1-6烷基，或R11和R12与带R11和R12的氮原子结合，可以形成取代为C1-6烷基，氨基或单或二(C1-6烷基)氨基的吡咯啉基或哌啶基环，或R11和R12与带R11和R12的氮结合，可以形成取代为C1-6烷基的哌嗪基或4-吗啉基基团。公开了制备这些产品的过程，包括这些产品的制剂及其作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。
• The use of 5ht4 receptor antagonists in the prophylaxis or treatment of certain cardiovascular conditions
  申请人：Bonhomme Marguerite Jeanne Mireille

  公开号：US20050032866A1

  公开（公告）日：2005-02-10

  The invention relates to the use of a 5-HT 4 receptor antagonist in the manufacture of a medicament for the prophylaxis or treatment of atrial remodelling in a mammal. Preferably, the antagonist is N-[(1- n butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide (SB 207266) or a pharmaceutically acceptable salt thereof. The invention also relates to the use of SB 207266 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment or prophylaxis of atrial fibrillation in a mammal by administering to the mammal a daily oral or parenteral dosage regimen of about 0.2 mg to 1.0 mg of the SB 207266 or salt thereof per kg of total body weight (measured as the free base). The invention also relates to the use of SB 207266 or a pharmaceutically acceptable salt thereof in the prophylaxis or treatment of atrial arrhythmia in a mammal by administration of the SB 207266 or salt thereof on the first day at a loading dose of about 1.2 to about 2.0 times the daily maintainance dose, followed by administration of the SB 207266 or salt at the daily maintainance dose on subsequent days.

  本发明涉及使用 5-HT 4 受体拮抗剂用于制造预防或治疗哺乳动物心房重塑的药物。优选地，拮抗剂是 N-[（1- n 丁基-4-哌啶基）甲基]-3,4-二氢-2H-[1,3]恶嗪并[3,2-a]吲哚-10-甲酰胺（SB 207266）或其药学上可接受的盐。本发明还涉及 SB 207266 或其药学上可接受的盐在制造用于治疗或预防哺乳动物心房颤动的药物中的用途，方法是向哺乳动物施用每日口服或肠外剂量方案，每公斤总重量（以游离碱计）约 0.2 毫克至 1.0 毫克 SB 207266 或其盐。本发明还涉及SB 207266或其药学上可接受的盐在预防或治疗哺乳动物房性心律失常中的用途，方法是第一天以约1.2至约2.0倍每日维持剂量的负荷剂量给药SB 207266或其盐，随后几天以每日维持剂量给药SB 207266或其盐。
• Treatment of lower urinary tract symptoms associated with overactive bladder in men and women
  申请人：Jones Richard Charles

  公开号：US20050261344A1

  公开（公告）日：2005-11-24

  This invention relates to pharmaceutical combinations suitable for treating the lower urinary tract symptoms associated with either overactive bladder or mild to moderate benign prostatic hyperplasia, which combinations contain an alpha-adrenoceptor antagonist and a 5-HT 4 antagonist. The combinations of the invention are particularly suitable for treating moderate or severe symptomatology.

  本发明涉及适用于治疗与膀胱过度活跃症或轻度至中度良性前列腺增生症相关的下尿路症状的药物组合，这些组合含有一种α-肾上腺素受体拮抗剂和一种5-HT 4 拮抗剂。本发明的复方制剂尤其适用于治疗中度或重度症状。
• Pharmaceutical composition for treating and/or preventing a pathology associated with an obsessional behavior or with obesity
  申请人：Compan Valerie

  公开号：US20060116341A1

  公开（公告）日：2006-06-01

  This invention relates to the use of a ligand of the 5-HT 4 receptor or of a pharmaceutically acceptable salt of this ligand and to a nucleic acid coding for a 5-HT 4 receptor or of a functionally equivalent receptor for a drug for treating and/or preventing a pathology associated with an obsessional behavior such as anorexia, bulimia and the addiction to drugs of abuse or obesity. The invention also relates to a method for identifying a compound that is biologically active in the treatment and/or the prevention of a pathology associated with an obsessional conduct or obesity including: a) placing the 5-HT 4 receptor or a functionally equivalent receptor in contact with this biologically active compound, and b) the determination of whether this biologically active compound is capable of modulating the basal activity of the 5-HT 4 receptor or of a functionally equivalent receptor.

  本发明涉及一种 5-HT 4 受体的配体或该配体的药学上可接受的盐，以及编码 5-HT 4 受体或功能等效受体的核酸，用于治疗和/或预防与强迫行为有关的病理，如厌食症、贪食症和滥用药物成瘾或肥胖症。本发明还涉及一种鉴定化合物的方法，该化合物在治疗和/或预防与强迫行为或肥胖症相关的病理方面具有生物活性，包括：a) 将 5-HT 4 受体或功能相当的受体与这种生物活性化合物接触，以及 b) 确定这种生物活性化合物是否能够调节 5-HT 4 受体或功能相当的受体的基础活性。